Fibroblasts established in culture from skin biopsies have cell surface receptors for the polypeptide hormones, insulin and somatomedin. We have identified the first selective genetic defect of insulin receptors in fibroblasts cultured from a patient with leprechaunoid appearance, intrauterine growth retardation, and clinical insulin resistance. These results suggest a major role for insulin and insulin receptors in intrauterine growth. In our studies of the insulin-like growth factor (somatomedin) multiplication stimulating activity (MSA), a polypeptide synthesized by a cloned line of rat liver cells (BRL 3A), progress has been made in the following areas: 1) characterization of a polypeptide biochemically and immunologically related to BRL-MSA and synthesized by explants of fetal rat liver; 2) demonstration of 20- to 100-fold increased levels of MSA in fetal rat serum; 3) characterization of growth hormone-dependent binding proteins for somatomedins in serum of rats and humans; and 4) direct demonstration that acute metabolic effects of MSA and insulin, but not thieir long-term mitogenic effects, are mediated by insulin receptors.